Antti Tikkakoski

Analysis of cardiovascular responses to passive head‐up tilt using continuous pulse wave analysis and impedance cardiography

Objective. To non‐invasively measure central haemodynamics, arterial stiffness, cardiac function and vascular resistance, with the subject in the supine position and during head‐up tilt, in order to examine the haemodynamic changes associated with alterations in the augmentation index, and to investigate repeatability and reproducibility of the measurement protocol. Material and methods. Thirty‐three healthy volunteers (21–51 years) were investigated using continuous pulse wave analysis from the radial artery with a tonometric sensor, whole‐body impedance cardiography and plethysmographic blood pressure (BP) recordings from the fingers. The measurements were performed with the subject supine and during passive head‐up tilt, and repeated during the same session and on four separate days. Results. During the head‐up tilt, diastolic BP (5.2±0.6 %), heart rate (27.6±1.9 %) and vascular resistance (12.5±1.7 %) increased (all p<0.05), while systolic BP (−3.2±0.6 %), aortic pulse pressure (−23.3±1.4 %), augmentation index (−11.6±0.7 %), aortic reflection time (−7.0±1.0 %), ejection duration (−21.4±0.7 %), stroke volume (−26.1±1.2 %) and cardiac output (−5.0±1.5 %) decreased (all p<0.05). Augmentation index at rest correlated with aortic systolic BP (r = 0.423), aortic reflection time (r = −0.647), pulse wave velocity (r = 0.287) and age (r = 0.480). The change in augmentation index during head‐up tilt correlated with the change in aortic systolic BP (r = 0.469), aortic pulse pressure (r = 0.606), ejection duration (r = 0.374) and heart rate (r = −0.445). According to Bland‐Altman and repeatability index analyses, repeatability and reproducibility of the measurements were good during the same session and on separate days. Conclusions. Combined pulse wave analysis and impedance cardiography with the subject in the supine position and during head‐up tilt is a repeatable and reproducible method for comprehensive investigation of the cardiovascular function.

Metabolic syndrome may be associated with increased arterial stiffness even in the absence of hypertension: A study in 84 cases and 82 controls

OBJECTIVE To evaluate the hemodynamic characteristics of metabolic syndrome (MetS) in the absence and presence of hypertension. MATERIALS/METHODS Altogether 166 subjects without previously diagnosed cardiovascular disease, diabetes, or antihypertensive medication, were allocated to four groups: control, hypertension only, MetS without hypertension, and MetS with hypertension (mean age 44-46 years). Cut-point for hypertension was blood pressure ≥140/90 mmHg. Other criteria of MetS were as defined by Alberti et al. 2009. Hemodynamic variables were measured using whole-body impedance cardiography and pulse wave analysis. RESULTS Pulse wave velocity was higher in hypertensive and normotensive subjects with MetS than controls (p<0.05), and in the hypertensive MetS group than subjects with hypertension only (p<0.05). Aortic pulse pressure was higher in the two hypertensive groups than the two normotensive groups (p<0.05). Systemic vascular resistance index was higher in the hypertensive than normotensive MetS group (p<0.05), and in the group with hypertension alone than in controls (p<0.05). Heart rate was higher in the hypertensive Mets group than in controls and subjects with hypertension only (p<0.05). Cardiac index did not differ, while stroke index was lower in both groups with MetS than groups without MetS. Augmentation pressure was higher in the hypertensive MetS group than in controls and normotensive MetS group (p<0.05). CONCLUSIONS Pulse wave velocity, an acknowledged marker of arterial stiffness, was associated with MetS even in the absence of hypertension. This emphasizes the importance of the prevention and treatment of MetS.

Hemodynamic alterations in hypertensive patients at rest and during passive head-up tilt

Objective: Hypertension is characterized by increased vascular resistance and arterial stiffness, but information about upright hemodynamics is scarce. We compared hemodynamics in hypertensive versus normotensive patients at rest and during passive head-up tilt. Methods: Volunteers (n = 387, 19–72 years) without antihypertensive medication were recorded using continuous tonometric pulse wave analysis and whole-body impedance cardiography. Seated office blood pressure was 4/10 mmHg (systolic/diastolic) higher than average supine values during hemodynamic measurements. As there is no accepted cut-off for hypertension during tilt-table tests, supine level at least 135/85 mmHg defined hypertension (n = 155) versus normotension (n = 232). Age, BMI, and proportion of men were higher among hypertensives (49 vs. 42 years, 28 vs. 25, 55 vs. 38%, respectively), and analyses were adjusted for these differences. Results: Both at rest and during head-up tilt radial and aortic blood pressure and pulse pressure, cardiac index (CI) and work, systemic vascular resistance (SVR), and augmentation pressure were higher in hypertensive patients (P < 0.05 for all). Adjusted linear regression analyses showed that during passive head-up tilt aortic SBP and pulse pressure, stroke index, and left cardiac work index decreased less; heart rate increased less; and aortic DBP and SVR increased more in hypertensive patients (P < 0.05 for all); whereas reduction in CI and augmentation index did not differ between the groups. Conclusion: Not only supine hemodynamics, but also responses to head-up tilt differed between normotensive and hypertensive patients, indicating functional alterations beyond increased vascular resistance and higher arterial stiffness in hypertension.

Supine and upright haemodynamic effects of sublingual nitroglycerin and inhaled salbutamol: a double-blind, placebo-controlled, randomized study.

Objectives: Pulse wave analysis is widely applied to measure the haemodynamic effects of nitroglycerin and salbutamol as an endothelium-independent and endothelium-dependent vasodilator, respectively. The recordings are usually performed in supine position from 10 to 20 successive heartbeats without simultaneous measurement of vascular resistance and cardiac function. Our objective was to examine the effects of nitroglycerin and salbutamol on central haemodynamics, arterial stiffness, cardiac function, and vascular resistance in supine and upright positions. Methods: A placebo-controlled, randomized and double-blinded passive head-up tilt protocol was performed after sublingual nitroglycerin (0.25 mg) or inhaled salbutamol (400 &mgr;g) in 35 healthy volunteers. Continuous tonometric pulse wave analysis, whole-body impedance cardiography, and plethysmographic finger blood pressure recordings were applied. Results: Nitroglycerin decreased aortic and finger blood pressure, radial DBP, vascular resistance, augmentation index and pulse wave velocity, and increased heart rate, cardiac index, stroke index and aortic reflection time (P < 0.030 for all). Salbutamol moderately decreased radial and aortic blood pressure and finger DBP, augmentation index and vascular resistance, but increased heart rate and cardiac index (P < 0.030 for all). Almost all of the strong haemodynamic effects of nitroglycerin were emphasized during the head-up tilt, whereas the effects of salbutamol on heart rate and cardiac index were more pronounced in the supine position. Conclusion: The haemodynamic changes induced by nitroglycerin and salbutamol were dependent on body position: the effects of nitroglycerin were accentuated during the head-up tilt, whereas those of salbutamol were more evident in the supine position.

Central wave reflection is associated with peripheral arterial resistance in addition to arterial stiffness in subjects without antihypertensive medication

BackgroundAugmentation index, a marker of central wave reflection, is influenced by age, sex, height, blood pressure, heart rate, and arterial stiffness. However, the detailed haemodynamic determinants of augmentation index, and their relations, remain uncertain. We examined the association of augmentation index with vascular resistance and other haemodynamic and non-haemodynamic factors.MethodsBackground information, laboratory values, and haemodynamics of 488 subjects (239 men, 249 women) without antihypertensive medication were obtained. Indices of central wave reflection, systemic vascular resistance, cardiac function, and pulse wave velocity were measured using continuous radial pulse wave analysis and whole-body impedance cardiography.ResultsIn a regression model including only haemodynamic variables, augmentation index in males and female subjects, respectively, was associated with systemic vascular resistance (β = 0.425, β = 0.336), pulse wave velocity (β = 0.409, β = 0.400) (P < 0.001 for all), stroke volume (β = 0.256, β = 0.278) (P = 0.001 for both) and heart rate (β = −0.150, β = −0.156) (P = 0.049 and P = 0.036). When age, height, weight, smoking habits, and laboratory values were included in the regression model, the most significant explanatory variables for augmentation index in males and females, respectively, were age (β = 0.577, β = 0.557) and systemic vascular resistance (β = 0.437, β = 0.295) (P < 0.001 for all). In the final regression model, pulse wave velocity was not a significant explanatory variable for augmentation index, probably due to the high correlation of this variable with age (Spearman’s correlation ≥0.617).ConclusionAugmentation index is strongly associated with systemic vascular resistance in addition to arterial stiffness.Trial registrationClinicalTrials.gov, NCT01742702.

Daily Liquorice Consumption for Two Weeks Increases Augmentation Index and Central Systolic and Diastolic Blood Pressure

Background Liquorice ingestion often elevates blood pressure, but the detailed haemodynamic alterations are unknown. We studied haemodynamic changes induced by liquorice consumption in 20 subjects versus 30 controls with average blood pressures of 120/68 and 116/64 mmHg, respectively. Methods Haemodynamic variables were measured in supine position before and after two weeks of liquorice consumption (daily glycyrrhizin dose 290–370 mg) with tonometric recording of radial blood pressure, pulse wave analysis, and whole-body impedance cardiography. Thirty age-matched healthy subjects maintaining their normal diet were studied as controls. Results Two weeks of liquorice ingestion elevated peripheral and central systolic and diastolic blood pressure (by 7/4 and 8/4 mmHg, 95% confidence intervals [CI] 2-11/1-8 and 3-13/1-8, respectively, P<0.05), and increased extracellular volume by 0.5 litres (P<0.05 versus controls). Also augmentation index adjusted to heart rate 75/min (from 7% to 11%, 95% CI for change 0.3-7.5, P<0.05) and aortic pulse pressure (by 4 mmHg, 95% CI 1-7, P<0.05) were elevated indicating increased wave reflection from the periphery. In contrast, peripheral (−3/−0.3 mmHg) and central blood pressure (−2/−0.5 mmHg), aortic pulse pressure (−1 mmHg), and augmentation index adjusted to heart rate 75/min (from 9% to 7%) decreased numerically but not statistically significantly without changes in extracellular volume in the control group. Heart rate, systemic vascular resistance, cardiac output, and pulse wave velocity did not differ between the groups. Conclusions Two weeks of daily liquorice consumption increased extracellular volume, amplified pressure wave reflection from the periphery, and elevated central systolic and diastolic blood pressure. Trial Registration EU Clinical Trials Register EudraCT 2006-002065-39 ClinicalTrials.gov NCT01742702

Increased Cardiac Workload in the Upright Posture in Men: Noninvasive Hemodynamics in Men Versus Women

Background Men and women differ in the risk of cardiovascular disease, but the underlying mechanisms are not completely understood. We examined possible sex‐related differences in supine and upright cardiovascular regulation. Methods and Results Hemodynamics were recorded from 167 men and 167 women of matching age (≈45 years) and body mass index (≈26.5) during passive head‐up tilt. None had diabetes mellitus or cardiovascular disease other than hypertension or used antihypertensive medication. Whole‐body impedance cardiography, tonometric radial blood pressure, and heart rate variability were analyzed. Results were adjusted for height, smoking, alcohol intake, mean arterial pressure, plasma lipids, and glucose. Supine hemodynamic differences were minor: Men had lower heart rate (−4%) and higher stroke index (+7.5%) than women (P<0.05 for both). Upright systemic vascular resistance was lower (−10%), but stroke index (+15%), cardiac index (+16%), and left cardiac work were clearly higher (+20%) in men than in women (P<0.001 for all). Corresponding results were observed in a subgroup of men and postmenopausal women (n=76, aged >55 years). Heart rate variability analyses showed higher low:high frequency ratios in supine (P<0.001) and upright (P=0.003) positions in men. Conclusions The foremost difference in cardiovascular regulation between sexes was higher upright hemodynamic workload for the heart in men, a finding not explained by known cardiovascular risk factors or hormonal differences before menopause. Heart rate variability analyses indicated higher sympathovagal balance in men regardless of body position. The deviations in upright hemodynamics could play a role in the differences in cardiovascular risk between men and women. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01742702.

Effect of fermented milk product containing lactotripeptides and plant sterol esters on haemodynamics in subjects with the metabolic syndrome--a randomised, double-blind, placebo-controlled study.

We investigated the effects of fermented milk product containing isoleucine-proline-proline, valine-proline-proline and plant sterol esters (Pse) on plasma lipids, blood pressure (BP) and its determinants systemic vascular resistance and cardiac output. In a randomised, double-blind, placebo-controlled study, 104 subjects with the metabolic syndrome (MetS) were allocated to three groups in order to receive fermented milk product containing (1) 5 mg/d lactotripeptides (LTP) and 2 g/d plant sterols; (2) 25 mg/d LTP and 2 g/d plant sterols; (3) placebo for 12 weeks. Plasma lipids and home BP were monitored. Haemodynamics were examined in a laboratory using radial pulse wave analysis and whole-body impedance cardiography in the supine position and during orthostatic challenge. There were no differences between the effects of the two treatments and placebo on the measurements of BP at home or on BP, systemic vascular resistance index and cardiac index in the laboratory, neither in the supine nor in the upright position. The changes in plasma LDL-cholesterol concentration were - 0.1 (95% CI - 0.3, 0.1 and - 0.3, 0.0) mmol/l in the 5 and 25 mg/d LTP groups, respectively, and +0.1 (95% CI - 0.1, 0.3) mmol/l during placebo (P= 0.024). Both at baseline and at week 12, the increase in systemic vascular resistance during head-up tilt was lower in the 25 mg/d LTP group than in the 5 mg/d LTP group (P< 0.01), showing persistent differences in cardiovascular regulation between these groups. In subjects with the MetS, intake of LTP and Pse in fermented milk product showed a lipid-lowering effect of borderline significance, while no antihypertensive effect was observed at home or in the laboratory.

Lower Glomerular Filtration Rate Is Associated With Higher Systemic Vascular Resistance in Patients Without Prevalent Kidney Disease

The authors examined the association between estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine‐cystatin C equation, and hemodynamics in 556 normotensive or never‐treated hypertensive patients without kidney disease (mean age, 46 years). Hemodynamic variables were recorded using pulse wave analysis and whole‐body impedance cardiography. The mean eGFR was 98 mL/min/1.73 m2 (range, 64–145 mL/min/1.73 m2 and one third of the patients had values below 92, while none had proteinuria. In linear regression analyses adjusted for differences in age, weight:height ratio, low‐density lipoprotein cholesterol, and sex, significant associations were found between lower eGFR and higher systolic (P=.001) and diastolic blood pressure (P<.001) and higher systemic vascular resistance (P=.001). There was no association between eGFR and cardiac output or extracellular volume. In the absence of clinical kidney disease, lower eGFR was associated with higher blood pressure and systemic vascular resistance. Therefore, early impairment in kidney function may be involved in the pathogenesis of essential hypertension.

18-FDG-PET in a patient cohort suspected for cardiac sarcoidosis: Right ventricular uptake is associated with pathological uptake in mediastinal lymph nodes

Introduction In up to 65% of cardiac sarcoidosis patients, the disease is confined to the heart. Diagnosing isolated cardiac sarcoidosis is challenging due to the low sensitivity of endomyocardial biopsy. If cardiac sarcoidosis is part of biopsy-confirmed systemic sarcoidosis, the diagnosis can be based on cardiac imaging studies. We compared the imaging features of patients with isolated cardiac FDG uptake on positron emission tomography with those who had findings indicative of systemic sarcoidosis. Materials and methods 137 consecutive cardiac FDG-PET/CT studies performed on subjects suspected of having cardiac sarcoidosis were retrospectively analyzed. Results 33 patients had pathological left ventricular FDG uptake, and 12 of these also had pathological right ventricular uptake. 16/33 patients with pathological cardiac uptake had pathological extracardiac uptake. 10/12 patients with both LV- and RV-uptake patterns had extracardiac uptake compared to 6/21 of those with pathological LV uptake without RV uptake. SUVmax values in the myocardium were higher among patients with abnormal extracardiac uptake. The presence of extracardiac uptake was the only imaging-related factor that could predict a biopsy indicative of sarcoidosis. Conclusion Right ventricular involvement seems to be more common in patients who also have findings suggestive of suspected systemic sarcoidosis, compared with patients with PET findings indicative of isolated cardiac disease.